This invention relates to novel compositions of matter containing optically pure R-etodolac. These compositions possess potent activity in treating pain including, but not limited to, pain associated with toothaches, headaches, sprains, joint pain and surgical pain, for example dental pain and ophthalmic pain, while substantially reducing adverse effects associated with the administration of the racemic mixture of etodolac including but not limited to gastrointestinal, renal and hepatic toxicities, as well as leukopenia. Additionally, these novel compositions of matter containing optically pure R-etodolac are useful in treating or preventing pyrexia while substantially reducing the adverse effects associated with the administration of the racemic mixture of etodolac. Also disclosed are methods for treating the above-described conditions in a human while substantially reducing the adverse effects that are associated with the racemic mixture of etodolac, by administering the R-isomer of etodolac to said human.
The active compound of the present compositions and methods is an optical isomer of the compound etodolac, also known as etodolic acid, which is described in Humber, L. G. et al., J. Med. Chem. 29: 871-874 (1986); Humber, L. G. Medicinal Research Reviews 7(1): 1-28 (1987); and U.S. Pat. No. 3,843,681 and German Patent No. DE 2,226,340, both to Demerson et al. Chemically, this R-isomer is (-) 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid. This isomer will hereinafter be referred to as R(-) etodolac. This term also includes the substantially optically pure and optically pure R(-) etodolac isomer.
Etodolac, which is the subject of the present invention, is available commercially only as the 1:1 racemic mixture. That is, it is available only as a mixture of optical isomers, called enantiomers. The racemic mixture of etodolac is commercially available under the trade names ULTRADOL.RTM. and LODINE.RTM. by Ayerst Laboratories, New York.